scholarly journals Xiao Yao San Improves Depressive-Like Behaviors in Rats with Chronic Immobilization Stress through Modulation of Locus Coeruleus-Norepinephrine System

2014 ◽  
Vol 2014 ◽  
pp. 1-10 ◽  
Author(s):  
Xiu-Fang Ding ◽  
Xiao-Hua Zhao ◽  
Yang Tao ◽  
Wei-Chao Zhong ◽  
Qin Fan ◽  
...  

Most research focuses on the hypothalamic-pituitary-adrenal (HPA) axis, hypothalamus-pituitary-thyroid (HPT) axis, and hypothalamus-pituitary-gonadal (HPGA) axis systems of abnormalities of emotions and behaviors induced by stress, while no studies of Chinese herbal medicine such as Xiao Yao San (XYS) on the mechanisms of locus coeruleus-norepinephrine (LC-NE) system have been reported. Therefore, experiments were carried out to observe mechanism of LC-NE system in response to chronic immobilization stress (CIS) and explore the antidepressant effect of XYS. Rat model was established by CIS. LC morphology in rat was conducted. The serum norepinephrine (NE) concentrations and NE biosynthesis such as tyrosine hydroxylase (TH), dopamine-β-hydroxylase (DBH), and corticotrophin-releasing-factor (CRF) in LC were determined. Results showed that there were no discernible alterations in LC in rats. The serum NE concentrations, positive neurons, mean optical density (MOD), and protein levels of TH, DBH, and CRF in model group were significantly increased compared to the control group. But XYS-treated group displayed a significantly decreased in NE levels and expressions of TH, DBH, and CRF compared to the model group. In conclusion, CIS can activate LC-NE system to release NE and then result in a significant decrease in rats. XYS treatment can effectively improve depressive-like behaviors in rats through inhibition of LC-NE neurons activity.

2011 ◽  
Vol 365 ◽  
pp. 216-221
Author(s):  
Mei Jing Kou ◽  
Da Cheng He ◽  
Pei Zhang ◽  
Jia Xu Chen ◽  
Shao Xian Wang ◽  
...  

To select differentially expressed proteins in hippocampus of rats with pattern of Liver Qi stagnation and Spleen deficiency (LQSSD) induced by chronic immobilization stress (CIS), by applying the technique of protein chip and surface-enhanced laser desorption ionization time of flight mass spectrometry (SELDI-TOF-MS). Methods: The rats with pattern of LQSSD according to traditional Chinese medicine (TCM) were replicated by the method of CIS. After twenty-one days’ stress, the protein chip weak cation CM10 and SELDI-TOF-MS were applied in order to do mass spectral analysis of the proteins acquired from the three groups: normal control group, 21 days model group, and Xiaoyaosan (XYS) treatment group. Bio Marker Wizard software were adopted to analyze the differentially expressed proteins. Results: Five differentially expressed proteins were selected between the control group and model group, and they were all highly expressed in the model group. Thirteen one were selected between control group and treatment group, among which 3 were highly expressed in the treatment group, and 10 were highly expressed in the control group. Only 1 differentially expressed protein was selected between the treatment group and the model group and it was highly expressed in the latter. Conclusion: The differentially expressed proteins may be the specific marker proteins in hippocampus of rats with pattern of LQSSD induced by CIS. TCM formula XYS may be an effective intervention for protein expression in hippocampus of rats with pattern of LQSSD.


Author(s):  
Zafer Sahin ◽  
Alpaslan Ozkurkculer ◽  
Omer Faruk Kalkan ◽  
Ahmet Ozkaya ◽  
Aynur Koc ◽  
...  

Abstract. Alterations of essential elements in the brain are associated with the pathophysiology of many neuropsychiatric disorders. It is known that chronic/overwhelming stress may cause some anxiety and/or depression. We aimed to investigate the effects of two different chronic immobilization stress protocols on anxiety-related behaviors and brain minerals. Adult male Wistar rats were divided into 3 groups as follows ( n = 10/group): control, immobilization stress-1 (45 minutes daily for 7-day) and immobilization stress-2 (45 minutes twice a day for 7-day). Stress-related behaviors were evaluated by open field test and forced swimming test. In the immobilization stress-1 and immobilization stress-2 groups, percentage of time spent in the central area (6.38 ± 0.41% and 6.28 ± 1.03% respectively, p < 0.05) and rearing frequency (2.75 ± 0.41 and 3.85 ± 0.46, p < 0.01 and p < 0.05, respectively) were lower, latency to center area (49.11 ± 5.87 s and 44.92 ± 8.04 s, p < 0.01 and p < 0.01, respectively), were higher than the control group (8.65 ± 0.49%, 5.37 ± 0.44 and 15.3 ± 3.32 s, respectively). In the immobilization stress-1 group, zinc (12.65 ± 0.1 ppm, p < 0.001), magnesium (170.4 ± 1.7 ppm, p < 0.005) and phosphate (2.76 ± 0.1 ppm, p < 0.05) levels were lower than the control group (13.87 ± 0.16 ppm, 179.31 ± 1.87 ppm and 3.11 ± 0.06 ppm, respectively). In the immobilization stress-2 group, magnesium (171.56 ± 1.87 ppm, p < 0.05), phosphate (2.44 ± 0.07 ppm, p < 0.001) levels were lower, and manganese (373.68 ± 5.76 ppb, p < 0.001) and copper (2.79 ± 0.15 ppm, p < 0.05) levels were higher than the control group (179.31 ± 1.87 ppm, 3.11 ± 0.06 ppm, 327.25 ± 8.35 ppb and 2.45 ± 0.05 ppm, respectively). Our results indicated that 7-day chronic immobilization stress increased anxiety-related behaviors in both stress groups. Zinc, magnesium, phosphate, copper and manganese levels were affected in the brain.


Author(s):  
Honglin Qu ◽  
Ruilian Liu ◽  
Jiaqin Chen ◽  
Lan Zheng ◽  
Rui Chen

Objective: To investigate the role of aerobic exercise in inhibiting chronic unpredictable mild stress (CUMS) depressed mice hippocampal inflammatory response and its potential mechanisms. Methods: Fifty-four male eight-week-old C57BL/6 mice were divided as control group (CG) (18 mice) and model group (36 mice). Model group mice were treated with 13 chronic stimulating factors for 28 days to set up the CUMS depression model. Neurobehavioral assessment was performed after modeling. The mice in the model group were randomly divided into the control model group (MG) and the aerobic exercise group (EG), with 18mice in each group. The EG group carried out the adaptive training of the running platform: 10 m/min, 0° slope, and increased by 10 minutes per day for 6 days. The formal training was carried for 8 weeks with 10 m/min speed, 0° slope, 60 min/d, 6 d/Week. After the training, a neurobehavioral assessment was performed, and hippocampus IL-1β and IL-10 protein levels were detected by ELISA. RT–PCR was used to detect the expression of miR-223 and TLR4, MyD88, and NF-κB in the hippocampus. Western blot was used to detect the expression of TLR4 and phosphorylated NF-κBp65 protein in the hippocampus. Results: The hippocampus function of CUMS depression model mice was impaired. The forced swimming and forced tail suspension time were significantly prolonged, and inflammatory factors IL-1β were significantly increased in the hippocampus. Aerobic exercise significantly improves CUMS-depressed mice hippocampal function, effectively reducing depressive behavior and IL-1β levels, and increasing IL-10 levels. Besides, aerobic exercise significantly upregulates the expression level of miR-223 and inhibits the high expression of TLR4, MyD88, and NF-κB. Conclusion: Aerobic exercise significantly increases the CUMS-depressed mice hippocampus expression of miR-223, and inhibits the downstream TLR4/MyD88-NF-κB signaling pathway and the hippocampal inflammatory response, which contributes to the improvement of the hippocampal function.


Marine Drugs ◽  
2019 ◽  
Vol 17 (11) ◽  
pp. 633
Author(s):  
Huifan Liu ◽  
Sufen Li ◽  
Yuming Zhong ◽  
Jianliang Liu ◽  
Hui Liu ◽  
...  

In this study, the antioxidant components in co-culture of Chlorella pyrenoidosa and Yarrowia lipolytica (3:1 ratio) were confirmed as trypsin-hydrolyzed peptides (EHPs). The EHPs were composed of 836 different peptides with molecular weights ranging from 639 to 3531 Da and were mainly composed of hydrophobic amino acids (48.1%). These peptides showed remarkable protective effects against oxidative stress in HepG2, which may be attributed to their structures. Furthermore, the mRNA and protein levels of nuclear factor erythroid 2-related factor 2 (Nrf2) were significantly lower in the peptide-treated group than in the control group, suggesting that the antioxidant enzyme-coding genes were not activated. The EC50 value of three peptides in the EHPs were in the order of AGYSPIGFVR (0.04 ± 0.002 mg/mL) > VLDELTLAR (0.09 ± 0.001 mg/mL) > LFDPVYLFDQG (0.41 ± 0.03 mg/mL); these results agreed with the prediction of the model (R2 > 0.9, Q2 > 0.5). Thus, EHPs show potential as potent new antioxidant agents.


ISRN Urology ◽  
2013 ◽  
Vol 2013 ◽  
pp. 1-10 ◽  
Author(s):  
Gulsah Bitgul ◽  
Isil Tekmen ◽  
Didem Keles ◽  
Gulgun Oktay

Objective. The aim of this study was to investigate protective effects of resveratrol, a strong antioxidant, against possible negative effects of chronic immobilization stress on testes of male rats histochemically, immunohistochemically, ultrastructurally, and biochemically. Material and Methods. Male Wistar rats were divided into 4 groups (n=7). Group I, control group (C), was not exposed to stress. Group II, stress group (S), was exposed to chronic immobilization stress. In Group III, low dose resveratrol + stress group (LRS), rats were given 10 mg/kg/day resveratrol just before the stress application. In Group IV, high dose resveratrol + stress group (HRS), rats were given 20 mg/kg/day resveratrol just before the stress application. For chronic immobilization stress application animals were put in the plastic tubes (6 cm in diameter, 15 cm in length) during 32 days for 6 hours. All animals were sacrificed 18 hours after the last stress application. Results. Histochemical and ultrastructural investigations showed that in stress group there was germ cell deprivation in seminiferous tubules and increase of connective tissue on interstitial area. No significant changes were seen in low and high dose resveratrol groups. After immunohistochemical investigations, TUNEL (+) and Active Caspase-3 (+) cells were increased in seminiferous tubules of stress group compared with those control group, but they were decreased in low and high dose resveratrol groups. According to biochemically results, MDA, GSH, and testosterone levels in stress group showed no significant difference when compared with those of the other groups. Conclusion. The chronic immobilization stress increases oxidative stress and apoptosis and causes histological tissue damages; resveratrol can minimize the histological damage in testes significantly.


2020 ◽  
Vol 23 (7) ◽  
pp. 675-683
Author(s):  
Weijie Wang ◽  
Lingyong Cao ◽  
Xinchang Wang ◽  
Yongsheng Fan

Objective: Vasculitis is the basic pathological change of systemic lupus erythematosus (SLE). Radix Paeoniae Rubra (RPR), a traditional Chinese herb with the function of reducing blood stasis, has anti-inflammatory and immunoregulatory properties. This study explored the effects of RPR on the kidneys of lupus-like symptoms of mrl (MRL/lpr) mice from the perspective of intercellular cell adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1) and platelet endothelial cell adhesion molecule-1 (PECAM-1). Methods: Eighteen MRL/lpr lupus model mice were randomly divided into three groups, the model control group, prednisone-treated group, and RPR-treated group, and 6 C57BL/ 6 mice were classified as a control group. After the mice had been treated for 12 weeks, the expression of ICAM-1, VCAM-1 and PECAM-1in the kidney was determined by immunohistochemistry and Reverse Transcription-Polymerase Chain Reaction (RT-PCR). Results: After 12 weeks, there were significant differences in body weight in the model, prednisone and RPR groups compared with the normal group (P <0.05). Pathological observation: Compared with the model group, the proliferation of inflammatory cells infiltrated glomeruli and interstitial cells in prednisone and RPR groups were reduced, and renal pathological damage was reduced. Compared with the model group, urine protein level of prednisone and RPR groups were reduced with no significance (P> 0.05). The mRNA expression levels of ICAM-1 and VCAM-1 were significantly reduced in the prednisone group and RPR group compared with the model group (P <0.05 or P <0.01). Meanwhile, the immunohistochemistry expressions of ICAM-1 and VCAM- 1 expressed in the kidney were significantly reduced in the prednisone group and RPR group (P <0.01 or P <0.05). However, The mRNA expression level and the immunohistochemistry expressions of PECAM-1 expressed in the kidney were reduced in each treatment group (prednisone group and RPR group), but these differences were not significant (P>0.05). Conclusions: ICAM-1, VCAM-1 and PECAM-1 expression in the model group was found to be significantly increased. In addition, RPR could reduce the expression of ICAM-1, VCAM-1 and PECAM-1 in MRL/lpr lupus mice as effectively as prednisone, which may result in the dosage reduction of prednisone, thus decreasing the toxicity and improving the efficacy of prednisone - based treatment of SLE.


Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 4601-4601
Author(s):  
Dongmei He ◽  
Yuan Zhang ◽  
Gexiu Liu

Abstract Bcl-2 is the prominent member of a family of proteins responsible for dysregulation of apoptosis, and resistance to chemotherapy. It has been shown that reduction in Bcl-2 protein levels could ultimately induce a lower apoptotic threshold and restore chemosensitivity in a variety of malignancies. Short interfering RNA (siRNA) has been evaluated as an attractive and effective tool for suppressing a target protein by specifically digesting its mRNA. In our lab, we have identified a siRNA targeting against Bcl-2 could effectively down-regulate Bcl-2 protein. In this study, we investigated the effect of gamma radiation combined with the siRNA targeting Bcl-2 on proliferation and apoptosis in B-lymphoma Raji cells. The siRNA was introduced into cells using Oligofectamine transfection. Cells were treated with Bcl-2 siRNA alone or with 2–8 Gy dose of (60)Co gamma rays. Expression of Bcl-2 mRNA and protein was assayed by quantitative reverse transcriptase-polymerase chain reaction and Western blotting analysis. Radiosensitivity was determined by clonogenic cell survival assay. Apoptosis was determined by Giemsa staining, Annexin-V binding assay and flow cytomertry. Furthermore caspase-3 activity and poly (ADP-ribose) polymerase (PARP) cleavage were evaluated. Transfection of Raji cells with 100 nmol/L siRNA targeted against Bcl-2 resulted in reduction of Bcl-2 mRNA by 75% compared with control-siRNA treated group and the vehicle control group(p<0.05). The levels of Bcl-2 protein were significantly reduced by 70% compared with the two control groups (p<0.05). There was significant difference in the radiosensitivity of Raji cells in which Bcl-2 was silenced compared with the cells transfected vehicle or control siRNA.Apoptosis index of the Raji cells treated with Bcl-2 siRNA combined with radiation was significantly increased (p<0.05), compared with either control siRNA / radiation combination or radiation-treatment cells alone, or Bcl-2 siRNA-treatment cells alone.Raji cells treated with Bcl-2 siRNA combined with radiation revealed enhanced caspase-3 and PARP cleavage as compared to Bcl-2 siRNA treated cells alone or only irradiated cells. These findings show that Bcl-2 siRNA synergistically enhances radiation-induced apoptosis through the expression of proteins involved in the programmed cell death.


2013 ◽  
Vol 2013 ◽  
pp. 1-9 ◽  
Author(s):  
Zhanqiang Ma ◽  
Weiwei Ji ◽  
Rong Qu ◽  
Mingyan Wang ◽  
Wen Yang ◽  
...  

The aim of this study was to establish an experimental model for metabonomic profiles of the rat’s brain and then to investigate the antidepressant effect of Banxia Houpu decoction (BHD) and its possible mechanisms. Behavioral research and metabonomics method based on UPLC-MS were used to assess the efficacy of different fractions of BHD on chronic unpredictable mild stress (CUMS) model of depression. There was a significant difference between the BHD group and the model group. Eight endogenous metabolites, which are contributing to the separation of the model group and control group, were detected, while BHD group regulated the perturbed metabolites showing that there is a tendency of recovery compared to control group. Therefore, we think that those potential metabolite biomarkers have some relationship with BHD’s antidepression effect. This work appraised the antidepressant effect of Banxia Houpu decoction as well as revealing a metabonomics method, a valuable parameter in the TCM research.


2021 ◽  
Vol 2021 ◽  
pp. 1-9
Author(s):  
Hua Huang ◽  
Ping Zhao ◽  
Meijuan Xi ◽  
Fang Li ◽  
Lijiang Ji

To investigate the effect and mechanism of QingHuaZhiXie prescription on diarrhea predominant irritable bowel syndrome (D-IBS), animal models of rats were used in this study. 48 rats were randomly divided into 6 groups, containing one control group, one animal model group (D-IBS group), and four drug intervention groups (low, medium, and high dosage of QingHuaZhiXie prescription and trimebutine maleate intervention group). Abdominal withdrawal reflex (AWR) and Bristol stool form scale were recorded; the expression levels of inflammatory factors (TNF-α and IFN-γ), pathway proteins TLR4, MyD88, NF-κB, and key proteins of tight junction between intestinal epithelial cells (IECs) were detected; the microstructure of intestinal mucosal was observed by hematoxylin and eosin (H&E) staining; MPO activity was detected with immunohistochemical analysis to reflect the inflammation of tissues. Results show that QingHuaZhiXie prescription reduced diarrhea index and intestinal hypersensitivity and intestinal tissue integrity after intervention. MPO activity in QingHuaZhiXie prescription-treated rats was significantly lower relative to their model group. The expression levels of inflammatory factors and TLR4/MyD88/NF-κB pathway proteins were repressed, and the protein levels of occludin and claudin-1 increased. Meanwhile, this study also found that the remission effect of QingHuaZhiXie prescription on D-IBS increased with its dosage increase. Hence, as a therapeutic prescription for D-IBS, QingHuaZhiXie prescription could relieve D-IBS symptoms through balancing the inflammatory factors expression by inhibiting the TLR4/MyD88/NF-κB pathway and maintaining the function and structure of IECs by improving the protein levels of JAM, occludin, claudin-1, and ZO-1.


Vascular ◽  
2017 ◽  
Vol 26 (1) ◽  
pp. 18-26 ◽  
Author(s):  
Zhaojun Wang ◽  
Zhongqun Wang ◽  
Jie Zhu ◽  
Xinguang Long ◽  
Jinchuan Yan

Background and objectives Vascular calcification is a common complication in atherosclerosis. Accumulating evidence showed that Toll-like receptors (TLRs) mediate pro-inflammatory and atherosclerosis. Recent studies demonstrated that vascular calcification is one of the detrimental effects of vitamin K (Vit K) antagonists. However, the effects of Vit K on the expression of TLR2 and 4 and intimal calcification in artery remained unidentified. Methods and results Eighteen ApoE-/- mice were randomly divided into model group, Vit K-treated group, and control group. The mice of model and Vit K-treated group were fed with high-fat diet, while control group mice were fed with normal diet. Mice of Vit K-treated group were administered orally with vitamin K2 (40 mg.kg−1.day−1) for 12 weeks. Twelve weeks later the aortic sections of mice were acquired and stained with hematoxylin and eosin and von Kossa, respectively. Calcium content and activity of alkaline phosphatase (ALP) at aortic tissues were measured. The expression levels of TLR2 and TLR4 in aorta sections were detected by immunohistochemisty and RT-PCR, respectively. The effects of Vit K on cellular calcification were further studied in A7r5 SMCs. Results demonstrated that high-fat diet induced typical atherosclerosis with intimal calcification in ApoE-/- mice, while in Vit K-treated group atherosclerosis and calcium deposits were not serious; Vit K2 also inhibited cellular calcification in A7r5 SMCs. Quantitative analysis showed that calcium and ALP activity at aortic tissues in the Vit K-treated mice were significantly lower than that of the model group ( P < 0.01); Compared to the control group, the expression levels of TLR2 and TLR4 in the model group were significantly higher ( P < 0.05), while in Vit K-treated group the levels of TLR2 and 4 were significantly lower than that in the model group. Furthermore, the content of calcium was positively related to the expression levels of TLR2 and TLR4 mRNA at aortic tissues ( r = 0.77 and r = 0.79, respectively, both P < 0.001). Conclusion VitK2 can inhibit intimal calcification of aortic artery induced by high-fat diet in ApoE-/- mice and A7r5 SMCs calcification induced by β-sodium glycerophosphate, and meanwhile can reduce the expression of TLR2 and TLR4. These results suggested that the effects of VitK2 on vascular calcification may be associated with the expression of TLR2 and TLR4.


Sign in / Sign up

Export Citation Format

Share Document